The Annual Carrell-Krusen Neuromuscular Symposium is a unique conference attended by more than 200 each year in Dallas, Texas. Its name honors Dr. Brandon Carrell who retired as physician-in-chief at Texas Scottish Rite Hospital in 1978 and Dr. Ed Krusen who organized the first Muscular Dystrophy Association clinic in Dallas. This Symposium began in 1978 under the leadership of Dr. Jay Cook as a Muscular Dystrophy Clinic Directors' meeting and is now jointly sponsored by the hospital, the Muscular Dystrophy Association, Childrens' Medical Center of Dallas, and the University of Texas Southwestern Medical Center. The Symposium has grown to be the most popular clinical meeting for neuromuscular specialists in the country. During the 2 day meeting, attendees participate in lively discussions while meeting interesting and challenging patients. Attendees are invited to contribute interesting electrodiagnostic and histopathologic cases to review with the group. The visiting professor, the recipient of the Carrell-Krusen Award, gives the keynote lecture. Currently, the Program Director is Dr. Susan T. Iannaccone and Co-Directors Dr. Jaya Trivedi and Dr. Diana Castro.
This publication represents a key component of the live conference that has been approved for AMA PRA Category 1 Credit. The University of Texas Southwestern Medical Center is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. All final accreditation, credit designation, and disclosure information is available at https://cme.utsouthwestern.edu/rp2202a as well as the final conference registration materials.
Susan Iannaccone, MD
Jaya Trivedi, MD
Diana Castro, MD
Salman Bhai, MD
Anne-Marie Jones, MS, BSN, RN
Lauren Phillips, MD
Steven Vernino, MD, PhD
L/V-1 When Pes Cavus is not Charcot-Marie-Tooth
K. Alrasheed, N. Goyal, Irvine, CA.
Background: Pes cavus is a foot deformity characterized by a high arch of the foot that does not flatten with weight bearing; It can be seen in the general population, with a prevalence of approximately 10% due to musculoskeletal changes. It can also be seen in hereditary neuropathy, with Charcot-Marie-Tooth (CMT) being the most common hereditary neuropathy. When CMT is ruled out, other clinical features and extensive neurological exam must be sought to rule out other rare causes of inherited neuropathy.
Objective: To describe a rare cause of inherited peripheral neuropathy associated with pes cavus and hammer toes.
Method: Case report.
Results: A 21-year-old man who has a history of progressively worsening gait imbalance since 10 years of age. He denies numbness, paresthesias or weakness. He is adopted with unknown family history. His exam showed saccadic eye movements, scanning dysarthria, dysmetria, ataxic gait, pes cavus and hammertoes with preserved muscle strength and diffuse hyporeflexia. Sensory exam revealed decreased vibration and joint position sense distally. CK level was 1189 u/L. Alpha fetoprotein was elevated. EMG showed a severe axonal sensory > motor polyneuropathy. MRI showed cerebellar atrophy. Genetic testing was negative for the Inherited neuropathy panel (Invitae) and Spinocerebellar ataxia (SCA) panel (MNG). A diagnostic test was performed that revealed the diagnosis.
Conclusion: Inherited cerebellar ataxia syndromes can be commonly associated with peripheral neuropathy. Differential diagnosis of this combination includes ataxia telangiectasia, Friedrich ataxia, ataxia with oculomotor apraxia (AOA) type 1&2, SCA, autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), and Refsum disease. AOA type 2 (also called spinocerebellar ataxia, autosomal recessive, with axonal neuropathy type 2) is caused by homozygous mutations in the SETX gene, as seen in this patient. It is characterized by cerebellar ataxia, dysmetria and oculomotor abnormalities. Sensorimotor peripheral neuropathy is present in 93% of cases. Management is supportive.
L/V-2 Lifelong Diagnosis of a Functional Gait
S. Sheikhbahaei, N. Goyal, Orange, CA.
Objective: To describe a case of a rare inherited myopathy.
Case: A 70-year-old retired nurse presented with a lifelong gait disorder. She had delayed motor milestones, walked at 3 years, and was unable to run in school. In her 30's, she had trouble hiking. In her 50's, she required a walker, and in her 60's, a scooter for mobility. Her brother was diagnosed with IBM at an outside institution and paternal uncle required a scooter in his 50's. On exam, mild weakness noted with eye closure, neck flexion and symmetrical proximal arms and legs (MRC 4 to 4+), with dorsiflexor weakness. No scapular winging. Mild lumbar lordosis on standing, and camptocormia with walking.
Evaluation: CK 239 U/L. Muscle biopsy (2007): myopathy with many trabecular fibers. Myopathy gene panel (MNG 2016 and Perkin Elmer 2021) were unrevealing. MRI lumbar spine showed paraspinal muscle atrophy. FSHD genetic testing (2021) showed normal D4Z4 repeat number, but a permissive 4q35A allele and D4Z4 hypomethylation. However, SMCHD1 genetic testing (Perkin Elmer) was negative. A diagnostic test was performed.
Conclusion: The lack of an unrevealing workup since childhood led to the patient's eventual diagnosis of functional gait disorder prior to her referral to our center. Her exam was most significant for camptocormia which was overlooked. Myopathic causes of camptocormia or axial myopathy include: myotonic dystrophy, inclusion body myositis, FSHD1, select limb-girdle muscular dystrophies, sporadic late onset nemaline myopathy, Pompe disease, and VCP myopathy. The patient was ultimately diagnosed with FSHD2 after a pathogenic deletion was detected in SMCHD1 (Invitae) which was missed on Perkin Elmer testing due to the next generation sequencing technique, highlighting the importance of understanding the limitations of the different genetic tests available and describing a rare case of FSHD2 presenting with camptocormia.
L/V-3 Childhood Bulbar Dysfunction and Weakness
D. Stevens, T. Mozaffar, Irvine, CA.
A 12-year-old male with laryngomalacia since 6 months of age presents with progressive shortness of breath, dysarthria, and weakness since early childhood. His birth history is uncomplicated, other than congenital hearing loss and strabismus that underwent surgery. His speech is nasal, soft, and slowed. There is weakness in his arms more than legs. He has poor posture, and was diagnosed with scoliosis. He developed dysphagia around age 8 and diffuse muscle twitching at age 10. He has short stature for family and poor growth velocity. There is no known family history. Examination shows hypernasal speech and hypophonia. His eye movements are disconjugate with subjective diplopia. There is upper and lower facial weakness with perioral fasciculations. His tongue is weak, with atrophy and fasciculations. There is diffuse hypotonia, fasciculations, axial weakness, atrophy in proximal > distal muscles, bilateral scapular winging, and lordosis. He has proximal upper extremity and neck flexion weakness. His reflexes are absent and vibratory sense is diminished in his toes. Workup included forced vital capacity of 52% predicted, creatine kinase of 91, and MRI Brain with hypopituitarism. Nerve conduction studies showed neuropathy of the right ulnar nerve with conduction block. Repetitive stimulation was negative. Electromyography revealed neurogenic changes in the vastus lateralis and tibialis anterior muscles. Comprehensive neuromuscular panel and whole exome sequencing showed VUS in ARID1B and AGRN, which were deemed not causative. Facioscapulohumeral muscular dystrophy testing was negative. He underwent a trial of IV immunoglobulin therapy without benefit. The case appeared to localize best to a hereditary lower motor neuron disease, although testing for most known conditions such as Spinal Muscular Atrophy, Allgrove syndrome, Fazio-Londe, and Brown-Vialetto-Van Laere were all negative. A trial of Riboflavin replacement was still attempted with no improvement. Additional diagnostic testing was sent.
L/V-4 A Curious Case of Ptosis and Bulbar Weakness
J. Lin, S. Muppidi, S. Sakamuri, Palo Alto, CA.
An 82-year-old man was referred to the inpatient neuromuscular consult service due to 1 week of diplopia, ocular pain, ptosis, and bulbar weakness. The symptoms had developed and progressed rapidly, and in the day prior to admission, he developed slurred speech and difficulty with swallowing. This worsening prompted him to present to the emergency department. His neurological exam was notable for asymmetric ptosis, ophthalmoparesis, and eye closure weakness, all worse on the left. He had bilateral tongue weakness and bilateral facial weakness, with inability to puff out his cheeks or form a seal with his lips. Single breath counting was markedly abnormal and he was only able to count to 12. There was additional 4/5 weakness in neck flexion and finger abduction, and 4+/5 weakness in neck extension and hip flexion, with possible fatigability. He also demonstrated areflexia and length-dependent impaired to light touch, vibration, and pinprick up to the knees. This was attributed to known chemotherapy-induced neuropathy related to prior diagnosis of Sezary syndrome (T cell lymphoma), which was in remission. Urgent MRI brain with and without contrast was unrevealing. At the bedside, both the ice pack test and a pyridostigmine challenge resulted in improved ptosis. Anti-acetylcholine receptor and anti-muscle-specific tyrosine kinase antibodies were sent and were pending. Antibodies against HIV were not detectable. He was treated with intravenous immunoglobulin 2g/kg over 3 days. By day 3, there was unclear benefit.
L/V-5 Novel Target to Treat Congenital Hypotonia
N. Katz, S. Mackenzie, Rochester, NY.
A 3-year-old boy with a history of neonatal hypotonia and failure to thrive was seen in clinic. A neuromuscular gene panel that had previously been obtained at 5 months of age revealed a nonsense variant and a novel splice acceptor variant in a gene of interest known to be associated with neuromuscular disease. A variant of unknown significance was identified in a second gene known to be associated with congenital myopathy and hypertrophic cardiomyopathy. The patient has had normal cognitive development, to date, and attends mainstream pre-Kindergarten classes. Currently, he has antigravity movements of his upper but not the lower extremities. He has never been ambulatory but is able to independently operate a motorized wheelchair and can stand with a stander. He has contractures at the hips and knees and wears bilateral AFOs. He takes all food by mouth and has never received gastrostomy tube feeds. He is prescribed BiPAP but has issues with compliance. He has 10 degrees of scoliosis. The pathophysiology of this condition and potential gene-targeted therapeutic approaches will be discussed.
L/V-6 Developmental Delay & Supraventricular Tachycardia
A. Stanley-Copeland, Jackson, MS.
A.N. is an 8 year-old girl who presented for evaluation of developmental delays. She was born at 38 weeks gestation via vaginal delivery. Pregnancy was reportedly uncomplicated. Motor milestones were delayed, and she did not walk until 18 months of age. She was previously a toe walker. Speech and language were delayed as well. She was in Speech Therapy at school and had previously been in Physical Therapy and Occupational Therapy. She had to repeat kindergarten. Now she has an individualized education plan and is in both special & regular educational classes, as she continues to have difficulties learning. Of note, A.N. was diagnosed with supraventricular tachycardia at 7 years of age and required ablation but did not return to Cardiology clinic for follow-up after her procedure. A paternal aunt had learning difficulties/developmental delays as a child but now works offshore independently. On examination she was noted to be thin and short statured, but her head circumference was > 95th percentile. She had mild facial dysmorphism and a high palate. She had increased lordosis of her spine and scapular winging. Fund of knowledge was decreased for age. Speech and language were moderately delayed. Cranial nerve examination revealed weak eyelid closure. Muscle bulk and tone were decreased. She had difficulty following commands for manual motor testing but clearly had diffusely decreased strength. Reflexes were decreased. Fine motor movements in her hands were impaired. She had a one-handed Gower sign and a waddling gait. Her workup included an elevated creatine kinase of 1300+, normal brain MRI, and negative chromosomal microarray. A neuromuscular panel was diagnostic.
S-1 Frequency of Cancer in Myotonic Muscular Dystrophy
E. Silvana D'Ambrosio, P. Gonzalez-Perez, A. Amato, T. Wheeler, W. David, K. Chuang, Boston, MA.
Introduction: Myotonic dystrophy (DM) is the most common adult muscular dystrophy. Dominantly inherited CTG and CCTG repeat expansions in DMPK and CNBP genes cause DM type 1 and DM type 2, respectively. These genetic defects lead to abnormal splicing of different mRNA transcripts, responsible for the multiorgan involvement of these diseases. The frequency of cancer in DM patients appears to be higher than in other muscular dystrophies and the general population. An increased frequency of specific cancer types (thyroid, endometrium, ovary, skin, eye, brain, colorectal, and testis) has been reported in DM1 patients. The association between DM2 and cancer is less clear. Current consensus-based care recommendations advise, for DM patients, to follow the general cancer screening guidelines, but those do not include screening for some cancer types reported to be more frequent in DM patients.
Objective: To determine the frequency and type of cancers and benign tumors in our DM cohort of 168 DM1 patients and 56 DM2 patients.
Methods: A retrospective chart review of patients diagnosed with DM1 or DM2 from 2000 to 2020 at Massachusetts General Brigham was conducted. Demographics, clinical characteristics, and type of cancers and benign tumors, if present, were recorded.
Results: A total of 26 (15.5%) DM1 patients and 17 (30.3%) DM2 patients had at least one cancer, and 2 DM1 and 5 DM2 patients had more than one cancer. In addition to breast, skin and thyroid malignancies were the most frequent cancers in both DM1 and DM2 cohorts. Thyroid nodules were the most common benign tumor. Pilomatrixoma was only reported in one male DM1 patient.
Conclusion: In addition to cancer screening guidelines for the general population, and in alignment with other retrospective studies, DM patients may benefit from skin check and thyroid gland palpation as non-invasive and bedside tumoral screenings.
S-2 Pain Profile and Opioid Medication Use in Myositis
A. Bhashyam, M. Lubinus, E. Filmore, L. Wilson, J. Williams, O.Gonzalez Ramos, S. Bhai, Boston, MA.
Objectives: Pain is commonly reported in patients with myositis. This study assesses the presence of pain in the subtypes of myositis as well frequency of opioid and non-opioid pain medication use.
Methods: A survey was developed and distributed by Myositis Support and Understanding, a patient-led advocacy organization, to members of its group. Multivariate logistic regression analysis and chi-squared tests were performed.
Results: A total of 468 participants completed the survey. Four hundred twenty-three participants (dermatomyositis n = 183, polymyositis n = 109, and inclusion body myositis n = 131) were included, based on reported diagnosis, for final analysis. 91.5% of myositis patients reported current or past pain with 99% attributing their pain to myositis. There was a lower likelihood of pain in patients age over 60 years (OR 0.2, 95% CI: 0.1–0.6, P = 0.003). The percentage of patients reporting pain was statistically different based on myositis type (DM 97.2%, IBM 80.9%, and PM 94.5%, P < 0.001) with a higher likelihood of pain in DM compared to IBM (OR 3.7, 95% CI: 1.3–10.2, P = 0.011). There was a lower likelihood of pain in patients age over 60 years (OR 0.2, 95% CI: 0.1–0.6, P = 0.003). Of the 387 participants reporting pain, 335 reported using pain medications (69% prescribed opioids). Male sex, age over 60 years, and myositis subtype were not associated with likelihood of non-opioid use.
Conclusion: Pain is a commonly reported symptom in myositis with variable treatment strategies, including opioid medications. This study highlights the importance of addressing pain as part of myositis treatment as well as the need for future studies understanding treatment effectiveness.
S-3 Use of Mexiletine in Childhood Myotonic Dystrophy
S. Bivans, K. Ochoa Castro, S. Iannaccone, Dallas, TX.
Objective: To review our experience with the safety and effectiveness of the use of mexiletine in Myotonic Dystrophy type 1 (DM1) patients. Background: DM1 is a multisystem, dominantly inherited neuromuscular disease that is caused by a CTG expansion in the DMPK gene. Individuals with DM1 often develop problems in the gastrointestinal system including abdominal pain, constipation, diarrhea, and pseudo-obstruction which can be life threatening. Currently there is no treatment approved by the US FDA for gastrointestinal symptoms or myotonia in DM1. However, Mexiletine, a class 1B antiarrhythmic agent has been shown to be safe and effective in reducing grip myotonia in DM1.
Methods: This study was a retrospective chart review of all the patients seen at the MDA Care Center at Children's Health in Dallas, TX who carried a clinical diagnosis of DM1. We identified which patients had taken mexiletine and extracted data from their EHR regarding demographics, disease presentation, dose, duration of treatment, side effects, and response. We used descriptive biostatistics in order to explain both the effectiveness and safety of mexiletine in this population.
Results: Twelve out of the 73 total patients with DM1 took mexiletine over the course of their care at Children's. The treatment duration of mexiletine ranged from 1 month to 10 years and the dose ranged from 150 mg QOD to 295 mg BID. Nine out of the 12 patients responded very well and had slight-definite resolution of symptoms. Mexiletine was generally well tolerated. Three of the patients reported EKG changes during treatment, including atrial fibrillation, bradycardia, and tachycardia. Mild adverse events included fatigue and diarrhea.
Conclusions: Mexiletine has the potential to alleviate some of the most debilitating symptoms of low GI motility in DM1. The use of mexiletine seems to be safe in this population with recommended frequent monitoring.
S-4 Tendon Transfers in IBM: Systematic Review
A. Bhashyam, S. Bhai, Boston, MA.
Objective: To systematically assess the potential for tendon transfer surgery to improve hand function in inclusion body myositis (IBM) patients.
Data Sources: The databases of PubMed, CINAHL, and MEDLINE were searched from inception to December 2021 for studies of inclusion body myositis and tendon transfers. Two investigators independently selected studies.
Data Extraction: Standardized data abstraction was used to extract surgical technique and measures of hand function. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRIMSA) reporting guideline was followed.
Main Outcomes: The main outcome was improvement in hand function (eg, patient reported outcome measures (PROMs), range of motion, pinch/grip strength, muscle grade). Recorded information included indications and tendon transfer techniques with post-operative protocol.
Results: Three case reports were analyzed. Indications for tendon transfer in all 3 cases involved grip/pinch strength limitations that affected quality of life (QOL). All patients had improvement in gross hand function for at least 2 years. In all 3 patients, wrist extensors were used to reconstruct finger flexors. Specific transfers included: (1) brachioradialis (BR) to FDP and extensor carpi radialis longus (ECRL) to FPL transfers, (2) BR to FPL and ECRL to FDP, and (3) ECRL to FPL and extensor carpi ulnaris to FDP. Post-operatively, patients were immobilized for 4 weeks prior to starting hand therapy. Standardized measures of hand function or QOL were not reported.
Conclusions and Relevance: In this systematic review, evidence is limited to case reports regarding the utility of tendon transfers in improving hand functions in IBM. However, tendon transfers are commonly used in orthopedics to treat muscle-tendon unit dysfunction and may provide a viable treatment option for some IBM patients. Given the limited amount of standardized data, we propose a surgical trial with systematic assessment of hand function with a hand exam, pinch and grip dynamometry, and PROMs.
S-5 Cardiomyopathy in Friedreich's Ataxia Patients
Y. Lee, J. Trivedi, P. Mammen, Dallas, TX.
Objective: The objective was to evaluate the severity of cardiomyopathy in Friedreich's ataxia (FRDA) patients and to assess whether there was a gender difference.
Background: The most common cause of death in FRDA patients is cardiac failure. Cardiac MRI has been demonstrated to be a more sensitive measure in the cardiovascular assessment of FRDA patients; however, studies using cardiac MRI are limited. Additionally, these studies have not evaluated the role of sex in the development of cardiomyopathy in these patients.
Design/Methods: This study was a retrospective cohort study that consisted of 35 genetically confirmed adult patients (19 males and 16 females) followed in the UT Southwestern Neuromuscular Clinic with 14 of the patients (8 males and 6 females) having undergone extensive cardiovascular assessment. Variables collected include demographics, cardiovascular data, and neurologic parameters, which were measured in median and interquartile ranges.
Results: The median age of males and females was 26 years (21–36) and 30 years (20–38) respectively. The study revealed 57% of patients with late gadolinium enhancement (a marker of myocardial fibrosis) and 93% of patients with abnormal ECG findings, consistent with prior studies. FRDA patients who underwent cardiac MRI (n = 14) showed an increased interventricular septum diameter in females 1.5 cm (0.8–1.9) versus males 1.0 cm (0.9–1.1), suggestive of hypertrophic obstructive cardiomyopathy. The LV ejection fraction in males [52% (41–64)] was lower than in females [73% (69–73)]. The LVEDV index in males [69.5 (62.4–81.2)] was higher than in females [58.3 (46.5–63.1)].
Conclusion: Collectively, the current study revealed female FRDA patients are more prone to developing hypertrophic obstructive cardiomyopathy, while male FRDA patients develop dilated cardiomyopathy with depressed cardiac function. Future studies are focused on further defining the cardiovascular gender differences in order to better define the type of cardiomyopathy that develops in FRDA patients and thus initiate targeted medical therapies at an earlier age.
S-6 Myasthenia Gravis and COVID 19: Case series
V. Koneru, A. Shivaprasad, S. Shroff, Houston, TX.
Background: Till date, more than 49 million people have been affected by COVID 19. There are special concerns with regards to myasthenia gravis (MG) patients one is immune suppression increasing their susceptibility to infection and second infections exacerbating MG. We describe our experience with 17 MG patients who had COVID 19 and their outcomes.
Methods: Seventeen patients with MG who developed COVID 19 were identified from our database at Houston Methodist Hospital.
Results: Out of the 17, 15 patients had generalized MG and 2 patients had ocular MG. Twelve patients (70%) were hospitalized. Four patients (23%) died. Four patients recovered with residual COVID 19 related complications. Nine of the patients were on more than one immune suppressant medication. Seven patients (41%) had MG exacerbation. The type of immune suppressants and steroids did not seem to affect outcomes of COVID 19. Patients treated with intravenous immunoglobulin for MG exacerbation had variable COVID 19 outcomes.
Results: In our case series, 6 patients experienced MG exacerbation. The outcomes with relation to COVID 19 were variable and being on immune suppressants did not confer any benefit. The outcomes were not affected by the type of immune suppression.
S-7 Biking Induced Kinetic Electroshock Syndrome
A. Bhashyam, S. Bhai, Boston, MA.
A 33-year-old man with migraines presented for evaluation of intermittent burning, “electric” radiating inner thigh and groin pain while road cycling, unrelated to duration or intensity. This only occurred when he was fully seated while riding under a specific powerline. Orthopedic and neurologic exam were normal. Given the normal exam, we suspected an electromagnetic field played a role in this patient's presentation, thus we tested a permutation of 3 cyclists with 3 bicycles. Under the powerline in question, 2 cyclists experienced the “electric” sensation with all 3 bicycles, whereas the last cyclist did not experience the shock with any bicycle. The difference between the riders was that the unaffected rider had smaller diameter thighs that did not contact the saddle rails. With a multimeter, we measured 1.2 milliamps at the saddle rails when moving the bicycle through the field at 3.5 miles per hour. A cyclist is typically electrically isolated from the bicycle due to rubber handlebar grips, thus a differential charge can build up between the bike and the rider, effectively serving as a capacitor. With application of Ohm's law, current is discharged when the cyclist touches a conducting surface (eg, saddle rails), resulting in equalization of potentials across the gap of the cyclist and the bike. This microshock typically occurs on a small area of skin resulting in tingling or pain. We conducted a systematic review of PubMed database as well as searched Google., No peer-reviewed literature was found. Between 2006 and 2021, we identified 51 unique reports across 18 blog forums of cyclists describing microshocks in their groin or arm while traversing under high-voltage powerlines, which was often dismissed by clinicians and should be discussed in peer-reviewed literature. Thus, we present this small case series and dub this novel phenomenon BIKE syndrome.
B-1 POTS or Not? A Rare Diagnosis Mislabeled as POTS
J. Riecke, S. Vernino, Dallas, TX.
A 29-year-old woman presented to the autonomic clinic for evaluation and treatment of presumed postural orthostatic tachycardia syndrome (POTS). She reported at least 8 years of episodic dizziness. Episodes were initially predominately characterized by severe headache, sweating, and nausea and first occurred around age 21. At that time, she was a heavy alcohol user. Episodes would abate with sleep and initially occurred monthly but increased to every 1 to 2 weeks over the next few years. She also developed a new episode type, involving dizziness, lightheadedness, and pallor. This could be triggered by changes in position, such as standing up or bending forward, but would also occur randomly. About 3 years later she quit drinking alcohol and started regular exercise. This led to a reduced frequency of the episodes; however, they were still present. Prior to evaluation at our clinic, she started exercising less often, leading to an increased frequency in episodes. She had been evaluated for this complaint in a different city a few years before with diagnosis of hyperadrenergic POTS. She also had prior negative cardiology evaluation. General examination was notable for long limbs as well as finger and elbow joint hypermobility. Her neurologic examination was normal. Her resting supine BP was 130 s/80 s with HR ranging from 73 to 103. Standing HR increased to 144bpm. Autonomic testing showed normal autonomic reflexes except for a borderline E/I ratio during paced deep breathing. Tilt test showed an orthostatic drop in BP from 134/88 to 109/79 at 10 minutes of head-up tilt with a heart rate increment from 80 to 137 bpm. Initial blood and urine studies were sent and necessitated further imaging and genetic workup to establish a rare, and potentially life-threatening, systemic diagnosis.
B-2 Rapidly Progressing Myopathy in a Toddler
V. Vedanarayanan, J. Gibson, C. Cai, Austin, TX.
J.A., 17-month-old boy with progressive muscle weakness of 3 months duration. He was born to a 3 rd gravida mother. Pregnancy was uncomplicated. No perinatal problems. Head control by 3 months, sit unsupported 8 months and walk by 13 months. Lost ability to walk and lift leg against gravity by 14/15 months and inability to sit by 16/17 months. Developed swallowing difficulty and constipation. Social skills and speech were not affected. Serum ck was between 800 and 1500 IU. Whole exome test showed heterozygous VUS in COL6A3 gene and SLC52A2 gene. Weakness progressed to respiratory difficulty and dysphagia in few weeks requiring hospitalization. MRI brain showed mild T2 hyperintensity in medial thalamus and pons. CSF showed protein of 69 mg% with no cells. Echocardiogram was normal. MRI of muscles in both lower limbs showed abnormal T2 hyperintensity with no contrast enhancement. In the subsequent 2 months he ended with gastrostomy and tracheostomy with continuous ventilatory support. A muscle biopsy was performed.
B-3 A Rare Presentation of Inflammatory Myositis
J. Donnelly, A. Gilbert, R. Bhavaraju-Sanka, San Antonio, TX.
Brief Clinical History: We report the case of a 36-year-old woman with a past medical history of hypothyroidism, presenting with progressive descending weakness of all extremities. The patient had an inciting event of throat swelling after eating seafood, which was treated initially as an allergic reaction. However, over the course of the following 2 months, she developed increasing pain and weakness in her upper extremities and eventually the lower limbs, to the point she could no longer function independently. She developed diffuse anasarca, respiratory failure, dysphonia, and dysphagia, eventually requiring a gastrostomy tube. Neurology was consulted and recommended broad immunology workup, and the patient underwent trials of high-dose steroid, immunoglobulin, and plasmapheresis with limited improvement. In addition, the patient later developed a diffuse maculopapular rash on the arms, chest, and thighs.
Electrophysiological Studies: The needle study was limited by diffuse anasarca. Early recruitment and small motor units were noted in the right deltoid, consistent with a myopathic process.
Pathology & Radiology Results: Magnetic Resonance Imaging of the bilateral lower extremities, with and without contrast, was performed. T2 signal was increased in all visualized muscles, following along the fascial planes, without evidence of subfascial or intermuscular fluid accumulation. Diffuse skin thickening and subcutaneous inflammation were noted. Left deltoid muscle biopsy was performed. There was evidence of periarterial lymphocytic infiltrates, esterase-positive angular atrophic myofibers, and rare rimmed vacuoles, consistent with inflammatory myopathy and/or systemic vasculitis. Shave skin biopsy of the maculopapular rash was also performed. This demonstrated perivascular lymphocytic infiltrate, scattered necrotic keratinocytes and “basket-weave” orthokeratosis.
Conclusions: This report outlines a rare cause of rapidly progressive inflammatory myositis which was unfortunately resistant to immunotherapy. This case illustrates the need for prompt assessment and diagnosis in these patients so that targeted workup and therapy can be started as quickly as possible.
B-4 A Rare Cause of Progressive Myopathy
N. Anita Rau, A. Undavia, Philadelphia, PA.
A 72-year-old female presents with a sixteen-years-long-history of progressive weakness with recent worsening of symptoms, including falls. She reports difficulty with rising from a chair, squatting position, and recent arm weakness. She has ongoing dysphagia. She denies pain, fatigue, blurry/double vision. Patient was diagnosed with diabetes 1 year ago, and has been experiencing foot numbness for the past year. She has well controlled hyperlipidemia on atorvastatin for 15 years. General examination is unremarkable. Neurological examination is notable for bilateral lower extremity weakness, with quadriceps strength 4/5, plantar flexion 2/5, dorsiflexion 2/5, and steppage gait. Basic chemistries, CPK, Aldolase, ESR, and ACE were normal. ANA was negative. CT chest/abdomen/pelvis was negative. EMG showed diffuse irritable myopathy with normal sensory/motor responses. Quadriceps biopsy revealed non-necrotizing inflammatory granulomas with foci of atrophic myocytes. The differential diagnosis included a heterogenous group of inflammatory myopathies. Considering the absence of systemic findings/negative workup, we came to the final diagnosis. Patient was started on prednisone 60 mg daily for 2 weeks, followed by a taper of 40 mg thereafter. Patient experienced a 30%–40% improvement and was able to walk up the stairs. In spite of the improvement, patient could not tolerate steroids, and was started on methotrexate as a second line agent. She is concurrently being followed by rheumatology. We report a rare pathologically-diagnosed inflammatory myopathy. In a large scale study of 2985 biopsies, only 0.4% (12) revealed granulomatous inflammation. The most common differential, and more clinically reported entity, is also a rare diagnosis. The 2 entities share much in common, including age of onset (late), normal/mildly elevated CK, irritable myopathy on EMG, and non caseating granulomas on muscle biopsy. What makes our diagnosis is the lack of systemic findings, as well as association with another etiology.
B-5 Neuromuscular Disease Due to Checkpoint Inhibitor
J. Donnelly, A. Gilbert, R. Bhavaraju-Sanka, San Antonio, TX.
Brief Clinical History: We report the case of a 74-year-old woman with a past medical history of uterine cancer, recently started on pembrolizumab, presenting with chest pain, shortness of breath, generalized muscle weakness, myalgias, and fatigue. Cardiac evaluation was notable for myocarditis. On examination, the patient displayed bilateral fatigable ptosis, weakness of neck flexion and extension, and weakness of the proximal upper and lower extremities. A trial of pyridostigmine along with high-dose steroids and immunoglobulin was initiated, though the patient's course was complicated by sepsis and third-degree heart block requiring a pacemaker, so eventually, plasmapheresis was initiated. This resulted in some clinical improvement. Rituximab was initiated prior to discharge. Electrophysiological Studies: The right abductor pollicis brevis demonstrated −29.5% decrement after 2 minutes. On needle EMG, Polyphasia and short duration motor units were noted in the right deltoid, and increased recruitment was noted in the right deltoid, biceps, tensor fascia lata and vastus medialis oblique.
Pathology & Radiology Results: Magnetic resonance imaging bilateral femur without contrast: subcutaneous soft tissue swelling, fatty atrophic changes in thigh muscles with intermuscular edema. Muscle biopsy left vastus lateralis: lymphohistiocytic inflammatory aggregates, myofiber degeneration and necrosis with myophagocytosis, and severe type 2 myofiber atrophy.
Conclusions: This report outlines a rare cause of disabling autoimmune neuromuscular disease associated with checkpoint inhibitor use. This case demonstrates the need to recognize the potential autoimmune and/or neurological disorders that can be associated with these drugs, especially as use in oncology practice becomes more widespread.
B-6 Impaired Large Fiber Sensory Exam with Normal NCS
K. Hafeez, L. Sharp, F. Abid, Houston, TX.
A 19-year-old young woman initially presented to a neuromuscular clinic at the age of 9 years with symptoms of feeding difficulty since birth requiring a feeding tube, decreased tone since birth, weakness, delayed motor milestones, short stature, feet, and hand deformity, and difficulty walking in the dark. During the course of her disease, she developed severe scoliosis requiring surgery. Her swallowing gradually improved with no requirement of a feeding tube at the age of 18 years. Her exam showed normal cranial nerves, contractures at the elbows, hands, and feet, severe hallus valgus, pes planus, thumb subluxation, distal more than proximal muscle weakness ranging by Oxford scale from 2 to 5, impaired proprioception and vibration sensation with a normal light touch and temperature sensation, and a positive Romberg test. Deep tendon reflexes were graded as 0–1+ throughout. Her MRI brain was normal. Creatine Kinase was normal (69 U/L). Her electromyography and nerve conduction study showed normal conductions with no evidence of myopathic or neurogenic changes. For further evaluation, she underwent a muscle biopsy with findings of mild fiber size variation, increased mitochondrial proliferation, occasional fibers with increased lipid and glycogen, and occasional z-band irregularities. Her dystrophy panel was negative. She underwent mitochondrial next-generation sequencing (MitoNGS) which did not reveal any abnormality. She underwent Comprehensive Microarray Analysis and Whole Exome Sequencing (CMA and WES) which did not reveal any pathogenic variants to explain her condition. However, repeat analysis of WES was performed which revealed compound heterozygous mutations in a gene that encodes mechanosensitive ion channel previously reported to be associated with similar phenotype as our patient.
B-7 36-Year-Old Man with Episodes of Rhabdomyolysis
A. Hans, S. Bhai, Dallas, TX.
Episodes of rhabdomyolysis began 3 years prior to his evaluation. Prior to that, he was healthy and athletic, competitive in track and field and power lifting. He did, however, struggle with long distance sports where he had prominent fatigue. His first episode of rhabdomyolysis occurred with eccentric weightlifting. Since then, he had 3 more episodes. Cramps are more prominent then myalgias. Glucose intake prior to exercise does not impact activity. There is no second wind phenomenon. He does not worsen with fasting or fevers. He does not have contractures. There is no shortness of breath or chest pain. He does not have any ocular or bulbar symptoms. He does not have seizures or gastrointestinal issues. He does not have hearing loss. There is no family history of nerve, muscle, metabolic, or cardiac issues. He describes being born with a left ptotic eye, with a maternal nephew that also has this. He denies tobacco, alcohol, illicit drug use. He takes lisinopril. Work-up included normal non-fasting carnitine and acylcarnitine profile. Lactic acid, CK, and TSH were normal. EMG showed a chronic non-irritative proximal myopathy. MRI of bilateral femurs with contrast was normal. Gene testing for metabolic myopathy was negative. Limb-girdle muscular dystrophy panel had irrelevant variants of unknown significance (VUS). There was concern for a mitochondrial myopathy; however, mitochondrial genetic testing from the buccal mucosa showed a heterozygous VUS in POLG (nuclear DNA) and no mitochondrial DNA abnormalities. He then presented to the Institute for Exercise and Environmental Medicine for evaluation. On exam, he was of shorter stature. He did not have contractures. He had limited eye abduction bilaterally, left greater than right. He had left ptosis with left greater than right orbicularis oculi weakness. The remainder of his exam was normal including his strength exam. Diagnostic tests were then performed.
P-1 Phase 2/3 Study of Arimoclomol in IBM
P. Machado, M. Dimachkie, R. Barohn, M. McDermott, T. Lloyd, A. Shaibani, M. Freimer, A. Amato, E. Ciafaloni, London, England.
Objectives: To present efficacy and safety/tolerability data from phase 2/3 randomized controlled trial of arimoclomol in IBM (NCT02753530). Background: Since immune suppression is ineffective in inclusion body myositis (IBM), modulating the cytoprotective “heat shock response” (HSR) represents a candidate therapeutic approach targeting both inflammation and degeneration. In a pilot study, arimoclomol, an amplifier of the HSR, was safe and well tolerated with some trends suggesting efficacy at 8 months in subjects with IBM.
Methods: In this international multicenter, double-blind, controlled trial, subjects were randomized (1:1) to receive either arimoclomol citrate 400 mg TID or matching placebo for 20 months. Primary outcome measure was the change from baseline to Month 20 in the IBM Functional Rating Scale (IBMFRS). Key secondary outcome measures included hand grip strength (strongest hand), Modified Time Up and Go, Manual Muscle Testing, 6-minute walk distance, and Short-Form 36 health survey. Other outcome measures included patient and clinician impressions, and measures of muscle strength and function. Drug safety and tolerability were evaluated.
Results: One hundred fifty-two IBM subjects were randomized; mean age 67.2 years (SD8.1), mostly men (76%), mean disease duration 98 months (SD58), and mean baseline IBMFRS of 27.4 (SD4.6). The IBMFRS declined by a mean of 3.25 points with arimoclomol versus 2.26 points with placebo over 20 months (P = 0.11). Secondary efficacy outcome measures did not show any statistically significant treatment group differences. Most frequently reported AEs observed with higher incidence in arimoclomol group were gastrointestinal disorders. Patients receiving arimoclomol were more likely to discontinue treatment due to AEs. The relative frequency of serious AEs was comparable in the 2 treatment. Elevated transaminases were reported in the first 3 months and were more frequently observed with arimoclomol than with placebo.
Conclusions: This trial did not demonstrate a benefit of arimoclomol in IBM with respect to its primary and secondary efficacy endpoints.
P-2 An Unusual Case of Episodic Weakness
F. Du, L. Jenkins, Palo Alto, CA.
A 38-year-old woman presents with episodic leg weakness. Following normal development with normal motor milestones, she noted leg weakness following exertion or prolonged immobility from the age of 14. The issues have persisted with the development of mild distal weakness. Family history includes a maternal aunt and uncle diagnosed with hereditary spastic paraplegia, but no genetic confirmation is available and we have not been able to examine them. The proband's mother experiences mainly axial muscle tightness but is otherwise asymptomatic. The patient is otherwise well except for infertility with ovarian failure at age 38. Examination is notable for a distal symmetrical pure motor syndrome without spasticity, normal sensation, and brisk reflexes. Nerve conduction studies and EMG demonstrate a motor axonopathy/motor neuronopathy with normal sensory responses. There are no after discharges. MRI brain and spine are normal. Genetic testing including comprehensive neuromuscular panel and familial ALS panel are negative. The patient has declined muscle biopsy or trial of acetazolamide.
P-3 Patient and Physician Perspectives on gMG Care
K. Ruzhansky, N. Goyal, S. Muley, K. Richardson, D. Gelinas, T. Vu, Charleston, SC.
Purpose: To explore perceptions of generalized myasthenia gravis (gMG) care from the perspective of patients with gMG and physicians who treat gMG.
Methods: We conducted a cross-sectional study in May 2021 among U.S. adults with a self-reported gMG diagnosis and among physicians who treat gMG (patients and physicians were not matched pairs). We recruited respondents from online panels to complete surveys about gMG management and treatment. The study received IRB exemption.
Results: One hundred fifty-two patients with gMG and 250 physicians (neurologists, neuromuscular specialists, and neuro-ophthalmologists) completed online surveys. Most patients and physicians agreed that they make treatment decisions together (89% patients vs. 92% physicians), their relationship feels like a partnership (80% patients vs. 93% physicians), and physicians encourage patient participation in treatment discussions (78% patients vs. 94% physicians). Patients also agreed their physician was knowledgeable about gMG (91%) and had empathy and compassion regarding their condition (85%). However, over half of patients (54%) wished they had more time for in-depth discussions with their physician. Some patients believed their physician incorrectly thought their gMG symptoms were under control (28%) or their physician underestimates some of their symptoms (28%). Patients and physicians differed on reported frequency of conversations about gMG treatment topics: patients recalled discussions occurring less frequently than physicians regarding treatment adherence (53% of patients recalled discussing at most or all visits vs. 88% of physicians), side effects (56% patients vs. 84% physicians), and treatment administration (55% patients vs. 68% physicians).
Conclusions: Overall, patients are satisfied with the relationship and expertise of the physician who manages and treats their gMG. However, there is a mismatch between patient and physician perception regarding time spent discussing treatment adherence and toxicity, as well as disease control. Physician awareness of patient's perceptions can lead to changes in physician behavior and improvements in gMG care.
P-4 Same Story, Different Ending—Case Reports
V. Awori, S. Shukla, Jackson, MS.
Objective: Presentation of 7 case reports highlighting various etiologies of lower limb spasticity in a subset of patients attending the Neuromuscular clinic.
Methods: Chart Review.
Results: Case 1: Forty-four-year-old female patient, with SLE, who presented with symptoms of painless difficulty in walking, progressively worsening with onset at age 17. She had a VUS in the WASHC5 gene and is also being worked up for possible HSP. She is currently on treatment for SLE. Case 2: Forty-six-year-old female patient diagnosed to have SLE, who presented with bilateral lower limb weakness, difficulty in walking and increased urge in bowel and bladder function. Onset of symptoms was at the age of 44. Work up done was suggestive of lupus related myelopathy. Case 3: Thirty-six-year-old female patient, with a diagnosis of cerebral palsy. Onset of symptoms was at the age of 13, when she presented with gait imbalance, neck pain and distal paresthesias. Work up done was significant for degenerative disc C5 to C6 with central spinal stenosis and right foramina stenosis with no cord changes. Etiology is thought to be Cerebral palsy. Case 4: Sixty-four-year-old female patient with complaints of tightness of the feet, stiffness, and difficulty in walking. Onset was at 72 years of age. Work up revealed an uncertain GBA2 gene transcript change, and the etiology of the spasticity in this case is likely due to Parkinson's disease. Case 5: Seventy-six-year-old female patient with complaints of difficulty in walking, cramping, and twitching of the muscles as well as dysphagia. Lab studies were unremarkable, and NCS/EMG had no features of LMN disease. The working diagnosis is Primary Lateral sclerosis. Case 6:39-year-old female patient who presented with bilateral lower limb tightness, difficulty in walking and increasing fatigue. Onset of symptoms was at the age of 31. Laboratory studies were significant for GAD 65 antibody positive. She is currently being managed as a case of Stiff Person Syndrome. Case 7: Sixty-six-year-old male patient, who presented with back pain with radiation to both legs and subsequently bilateral lower limb weakness. The onset of symptoms was at the age of 54.NCS/EMG did not show evidence of large fiber neuropathy. Currently awaiting VUS testing in genes WASHC5 and SACS. Likely diagnosis in this case is a complex HSP type, with differential diagnosis of Primary Lateral Sclerosis.
Discussion: The above cases were patients who presented to the Neuromuscular clinic for work up of lower limb spasticity. After extensive history taking, a detailed clinical exam was performed in all the above cases. The common finding was increased lower extremity tone, hyperreflexia, and weakness in the lower extremities. Work up included lab studies for spastic paraparesis including HSP genes, VLFA, Heavy metals, HTLV and GAD 65 antibodies. Imaging studies entailed MRI of the brain and cervical and thoracic spine with and without contrast. Brain and spine imaging did not identify any lesion to explain the spasticity among the patients represented. Neurophysiologic tests were also done on most of the patients. Findings included mild axonal neuropathy, radiculopathy, and generalized motor neuronopathy. One of the patients, identified as case 3 is yet to have the NCS/EMG done.
Conclusion: This highlights the importance of genetic studies as well as other conventional studies in identifying the etiology even in patients with other comorbidities.
P-5 Limb-Girdle Weakness and Isolated Finger Extension
J. Luster, B. Jacobus, J. Sladky, T. Fullam, J. Jacobson, San Antonio, TX.
Background: We often have a script for the presentation of most neurologic disorders, including neuromuscular disorders. Consistent utilization of these scripts often allows for efficient and timely diagnosis. However, if a patient presents atypically, it can lead to diagnostic challenges and uncertainty in the case. As a result, utilization of additional testing modalities, such as electromyography/nerve conduction study, as an extension of the neurologic exam, can often provide clarity.
Results: The first case involves a 63-year-old male with history of recently diagnosed lung mass who presented for generalized weakness, upper extremities worse than lower extremities. Initially, there was concern for a myelopathy, which was unremarkable without evidence for cord compression. The patient became areflexic the following day prompting concern for Guillain-Barre Syndrome along with Lambert-Eaton Myasthenic Syndrome (LEMS), the latter due to his underlying lung mass. The second case involves an 83 yo male who presented with asymmetric right > left painless finger extension weakness for 2.5 months prior to initial evaluation. Initial concern was for cervical myelopathy versus motor neuron disease. For both patients, the decision was made to obtain an electromyography/nerve conduction study (EMG/NCS) and repetitive stimulation to better differentiate, which yielded unexpected results.
Conclusion: These cases illustrate the difficulty of diagnosing neuromuscular disorders solely based on exam given the wide array of presentations and clinical manifestations. They also demonstrate the utility and importance of EMG/NCS as an extension of the neurologic exam to the field of Neuromuscular Disorders.
P-6 Late Onset Neuropathy: Hereditary versus Acquired
S. Ambe, Houston, TX.
Background: A 48-year-old woman presented to the clinic complaining of weakness, numbness and tingling of extremities with a relapsing-remitting course. She has been receiving immunomodulatory therapies with varying degrees of clinical benefit.
Objective: To provide a brief overview of the investigation and diagnosis of hereditary relapsing-remitting neuropathies, including proposed mechanisms for steroid responsiveness.
Findings: Misdiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) and a new diagnosis of inherited demyelinating sensorimotor neuropathy.
Conclusion: Myelin protein zero (MPZ) gene mutation was detected on the neuropathy panel. MPZ related peripheral neuropathies can present with a relapsing-remitting course in adulthood and are characterized by slowly progressive distal muscle weakness with reports of steroid responsiveness in some cases. Hereditary neuropathies need to be considered in the differential diagnosis of relapsing-remitting neuropathies even in the setting of partial clinical benefit after immunomodulatory treatments.
P-7 Outcomes After PEG Intervention in ALS Patients
T. Fullam, S. Hunt, S. Chandrashekhar, O. Jawdat, B. Ghafari-Naraghi, E. Piccione, J. Americo Fernandes, R. Barohn, J. Statland, San Antonio, TX.
Objective: Determine whether malnutrition versus forced vital capacity (FVC) is predictive of early post-operative morbidity/mortality for percutaneous endoscopic gastrostomy (PEG).
Background: Practice parameters support PEG in ALS patients given benefits regarding weight stabilization and survival, despite increased periprocedural complications compared to other diseases. FVC less than 50% or malnutrition may be associated with mortality following PEG; however, these have not been consistently replicable.
Design/Methods: Retrospective review of clinically diagnosed ALS patients treated at 3 Midwest multi-disciplinary ALS clinics (University of Kansas, Nebraska, Missouri) from January 2009 to September 2020 referred for PEG. Data included demographics, disease characteristics, key PEG related dates/outcomes (PEG placement, hospital readmission post procedure, death and/or permanent ventilation). Standard descriptive statistics and one-way ANOVA were used for comparison. Data from University of Kansas was available for analysis.
Results: One hundred ninety-eight patients were included with median age of 65.5 years. Majority (54.5%) were female with bulbar onset ALS (58.6%). 30-day mortality was 4.5% (N = 9) and 30-day re-admission 8.1% (N = 16). Of those with 30-day mortality, 89% (N = 8) had weight loss greater than 10% from usual body weight (UBW). There was no difference in outcomes based on FVC less than 50% and BMI less than 18.5. Most common major complications included abscess and aspiration pneumonia (both N = 4, 2%) and minor complications were pain (N = 75, 38.1%) and tube migration (N = 25, 12.7%).
Conclusions: Rates of major/minor complications and 30-day mortality related to PEG were similar compared to prior studies in ALS. The increased 30-day mortality in those with greater than 10% UBW loss at time of PEG will have to be confirmed with additional site data. No difference in outcomes based on FVC may suggest improved perioperative management at PEG placement and/or alternative explanations for increased complications in ALS patients.
P-8 Delayed Diagnosis in Pediatric CMT
A. Veerapandiyan, V. Elumalai, Little Rock, AR.
Objective: To study the delay in diagnosis of Charcot Marie Tooth (CMT) disease in patients with and without known family history.
Study Design: Retrospective chart review of the patients with CMT disease followed in the neuropathy clinic at Arkansas Children's hospital. We analyzed the medical records of 54 patients to document the time course and steps taken to reach a definitive diagnosis.
Results: Our study population consists of 48% females. CMT type 1A type was the most common type (55%). In patients with family history of CMT disease, symptoms were first noted at a mean age of 3.7 years, and concerns were expressed to a primary care provider at a mean age of 5 years. Mean ages at the time of clinical diagnosis and genetic diagnosis were 7.2 years and 8 years respectively. In patients without a family history of CMT disease, symptoms were first noted at a mean age of 5.6 years, and concerns were expressed to a primary care provider at a mean age of 6.7 years. Mean ages at the time of clinical diagnosis and genetic diagnosis were 9.3 years and 10.3 years respectively.
Conclusion: There is delay of about 4 years between symptom onset and diagnosis in children with family history and the delay is about 5 years in children without family history. Symptoms were recognized at an earlier age in children with family history.
P-9 Acute Polyneuropathy in Patients with Weight Loss
I. Bakk, C. Farmakidis, M. Dimachkie, M. Pasnoor, Kansas City, KS.
Objective: Further define presentation, diagnosis, and management of acute to subacute nutritional neuropathy.
Background: A previous series characterized 13 women with acute length-dependent axonal neuropathy secondary to micronutrient deficiencies associated with poor nutritional status including prolonged vomiting and weight loss.
Design/Methods: Retrospective review of 14 patients evaluated at our center between January 2017 and September 2021 and diagnosed with acute onset nutritional neuropathy (1–4 weeks) and subacute onset (5–12 weeks).
Results: Thirteen patients were women, and one was a man. Mean age was 49. Nine patients had acute and 5 had subacute presentations. Four patients had a history of alcohol abuse. Five patients had preceding bariatric surgery. Five had a mental health condition. All patients had painful neuropathy with gait ataxia. Seven patients had vomiting. Six patients had at least a 10% weight loss. Three patients had only sensory symptoms. Eleven patients had motor and sensory manifestations. Micronutrient deficiencies identified include pyridoxine (8/11), thiamine (6/12), folate (5/13), B12 (4/14), copper (2/12), and vitamin E (2/12). Nine patients had multiple nutrient deficiencies; 1 patient had 4 deficiencies, 5 had 3 deficiencies, and 3 had 2 deficiencies. CSF protein was elevated in 2 of 11 patients, 95 and 99 mg/dL. NCS/EMG completed in 12 patients showed axonal neuropathy in 6 patients, mixed axonal and demyelinating neuropathy in 2 and was normal in 4. All axonal neuropathy patients had normal CSF protein. Four patients were treated with IVIG or steroids.
Conclusions: We found acute and subacute nutritional neuropathy has a strong female predominance and pyridoxine is the most common deficient nutrient. Most patients had 2 or more nutrient deficiencies highlighting the diagnostic yield of broader laboratory testing. In patients with acute and subacute axonal neuropathy in the setting of weight loss, vomiting, and demonstrated nutritional deficiencies, CSF testing appears to have limited utility.
P-10 Partially Purple Pedis Problem
A. Yaworski, R. Miller-Kuhlmann, S. Sakamuri, Palo Alto, CA.
A previously healthy 44-year-old man presented with several years of sensory changes in the feet. Symptoms began in 2017, when he abruptly developed pain and numbness on the lateral aspects of both feet and heels, occasionally involving the fourth and fifth toes. He described numbness, burning, and aching in this distribution, worse at the end of the day. The symptoms have persisted, though the numbness has improved slightly. Neurological examination showed reduced bulk in right extensor digitorum brevis (EDB), and reduced feeling to light touch in the lateral feet and toes 4 and 5 bilaterally, more so on the left. Strength, reflexes, and vibratory sensation were normal. In 2019, nerve conduction studies showed scattered and marked asymmetry: Peroneal motor response (recorded at EDB) was 1.8 mV on left, 7 mV on right. Sural sensory response was 3 uV on left, and 9 uV on the right. Superficial peroneal sensory responses were 4 uV bilaterally. Needle electromyography showed features of chronic reinnervation in bilateral tibialis anterior and gastrocnemius. MRI of the lumbar spine was normal. He recalls that around the time of symptom onset in 2017, he noted new purplish papules over the left shin and medial malleolus. These developed a hemorrhagic crust. He noted marked soreness of the distal shins in the absence of any trauma. Over months, the papules increased in number and became more painful, but would intermittently resolve. In retrospect he recalled 2 prior episodes of rash over the prior 12 years that were self-limited. Extensive laboratory testing for autoimmune and hematologic processes was unrevealing. This case highlights a rare cause of neuropathic pain, and emphasizes the importance of the dermatologic review of systems during the neuromuscular evaluation.
P-11 COVID Spike Antibodies in Neuromuscular Condition
A. Tajuddin, M. Pasnoor, M. Dimachkie, O. Jawdat, E. Ensrud, D. Jabari, C. Farmakidis, S. Chandrashekhar, A. Heim, Kansas City, KS.
Background: Little is known about the immune response to COVID vaccination in immune suppressed patient. A multiple studies showed variable data regarding the effect of immunosuppression on the immune response to the vaccination.
Objective: To report on COVID spike antibody levels in patients with various neuromuscular conditions who received vaccination and assess the effect of immunosuppressive therapies on antibody levels.
Methods: We performed a retrospective chart review on patients in neuromuscular clinic who had COVID antibody testing. We collected demographic, clinical and treatment information. Descriptive statistics was performed on the data obtained.
Results: One hundred six patient charts were reviewed to date. There were 53 male and 53 female included in this study. The mean age of the patients enrolled was 65.60 ± 14.51 and the mean duration of antibody acquisition since last date of vaccination was 156. High antibody titer >250 was seen in 61 patients (57.55%), low titer was seen in 32 patients (30.19%) and the antibody titer was not detected in 9 patients (8.49%). Four patients showed detected unmeasured antibody titer. From the 61 patients with high antibody titers 36 patients (59.01%) were on immunosuppressive medications compared to 26 of 32 patients (81.25%) with low antibody titer and 8 of 9 patients (88.88%) with undetected titer. Fifty percent of undetected antibody titer patients were on rituximab and around 23% of immunosuppressed patients in the low titer group were on azathioprine.
Conclusion: The analysis and enrolment of patients is still ongoing. Up till now around 60% of the patients on immunosuppressive drugs did develop adequate antibodies level against COVID-19 virus and around 80% of the low titer group were on immunosuppression.
P-12 Rare Cause of Brachial Diplegia
A. Ramzan, T. Nguyen, Houston, TX.
Introduction: “Man in a barrel” syndrome was coined by Sage in 1986 to describe weakness of the upper extremities, sparing the face and lower limbs. The syndrome is a misnomer, as males and females can be equally affected by the condition.
Methods: We report a rare, yet treatable, cause of bilateral upper extremity weakness with sparing of legs and face.
Results: An 18 year-old with Sweet's syndrome presented to our clinic due to 12 months of progressive worsening of neck pain, weakness and numbness of bilateral upper extremities both proximally and distally. Functionally, she could no longer lift a pencil to write at school or put on her backpack. She required assistance with many activities of daily living and was not attending school. Neurologic exam showed dense brachial diparesis, hyperreflexia and patchy sensory loss in arms. Electrodiagnostic testing showed acute and chronic neurogenic changes in multiple cervical roots with normal sensory and motor nerve conduction studies. MRI cervical spine showed large intra-medullary enhancing lesion in the cervical spinal cord extending from C2-3 through C6 associated with multiple flow voids mainly within periphery of the lesion but also extending through spinal canal. Angiogram was also performed that showed abnormal cervical spine blushing extending from C2 to C6 with evidence of arterial venous shunting. This cervical mass was resected with pathology depicting characteristic features of hemangioblastoma. Von Hippel Lindau was not tested due to financial reasons and low clinical suspicion. Onset of recovery was immediate with almost complete resolution of symptoms. One year later, she no longer required any assistance with activities of daily living and started working as a retail salesperson.
Conclusions: This case highlights a rare etiology of brachial diparesis in a young woman. The patient had significant functional improvement following treatment.
P-13 A Rare Cause of Acute Unilateral Foot Drop
J. Imbs, T. Nguyen, K. Sheikh, Houston, TX.
Introduction: Sciatic neuropathy is an important differential diagnosis in the setting of an acute foot drop and may be associated with a heterogenous group of disorders. We present a rare case of sciatic neuropathy secondary to a large lymphomatous lesion.
Methods: A 74-year-old female had undergone a left knee replacement in January 2020 with a subsequent non-traumatic fracture in early September 2020 resulting in surgical revision. Following the second procedure, the patient noted numbness and weakness in her distal left lower extremity that presented as a left footdrop.
Results: MRI left lower extremity in November 2020 showed a “large lobulated mass measuring approximately 19 cm encasing the posterior tibial neurovascular bundle and replacing much of the calf musculature.” The patient was hospitalized later that month with pneumonia and found to have stage 4 lymphoma involving her abdomen and left lower extremity. She underwent chemotherapy with Cytoxan, Rituxan, Adriamycin, Oncovin as well as intrathecal treatment with Cytarabine and Methotrexate and achieved full remission. She continued to have residual left footdrop. Focused neurologic examination in September 2021 revealed 0/5 left great toe dorsi/plantarflexion, 3+/5 left ankle dorsiflexion and inversion, 4/5 left knee flexion, and 4 + 5 left foot eversion. Decreased sensation to temperature and light touch was present distal to the left ankle. DTR 2 + bilateral patella, 1 + right Achilles, and absent at left Achilles. EMG/NCS revealed an early chronic, moderate to severe, axonal, left sciatic neuropathy proximal to the tibialis anterior, consistent with the patient's sensory deficits in the distal left lower extremity with left-sided foot drop.
Conclusions: This case highlights a rare cause of sciatic neuropathy as a consequence of a large lymphomatous lesion.
P-14 Genetic Polyneuropathy
D. French, S. Biliciler, Houston, TX.
Chronic polyneuropathies carry a diverse differential diagnosis that includes acquired and genetic etiologies. Herein we present a case of a 70-year-old male who presented to the clinic for further evaluation of his longstanding chronic inflammatory demyelinating polyneuropathy (CIDP) diagnosis. He had been treated with scheduled IVIG and later plasma exchange but continued to report progressive weakness. On exam, he demonstrated a length-dependent sensory loss in all extremities, reduced reflexes, and decreased strength in all extremities, especially in his proximal arms. Recent electrodiagnostic studies showed a diffuse sensorimotor axonal and demyelinating polyneuropathy. Laboratory testing showed an elevated creatine kinase level of 895 and a pathological mutation on his genetic panel. Muscle biopsy revealed severe neurogenic atrophy with secondary myopathic changes. The patient was given a new diagnosis for his genetic condition, resulting in his plasma exchange therapy cessation. With the expansion of genetic panels in recent years, further consideration and lab testing are warranted in neuropathy patients whose clinical course and presentation do not fit their current diagnosis neatly.
P-15 Effects of Cocaine on Peripheral Nervous System
H. Berry, M. Zulfiqar, S. Shukla, Jackson, MS.
Background: Peripheral neuropathies are characterized by damage and destruction of nerves that typically manifests as numbness, tingling, muscle weakness, and pain. Neuropathies can be due to many different etiologies, including systemic autoimmune inflammation, acquired demyelinating diseases, inherited disease, toxin exposure, and often lead to permanent and irreversible neurologic deficits.
Design/Methods: Case Report.
Results: Thirty-eight-year-old female with a history of cocaine abuse, schizophrenia and recent motor vehicle accident resulting in pelvic injuries and abscess presented with fever, tachycardia, hypertension, hyperreflexia in lower limbs with clonus and elevated Creatinine Kinase (CK). She was taking lithium and had recently discontinued olanzapine. Her symptoms persisted despite antibiotic treatment and lithium discontinuation. She was thought to have serotonin syndrome and symptoms improved with use of clonazepam. Patient then developed subacute asymmetric weakness in left proximal left lower limb (MRC 2/5) and right distal lower limb (MRC 4/5) along with reduced pinprick sensation in right superficial peroneal, left saphenous and femoral segments. Patient had elevated Erythrocyte sedimentation rate (ESR), C - reactive protein (CRP) but normal C3 and C4 complement levels and negative anti-Double stranded DNA (anti-DsDNA), anti-nuclear antibody (ANA) and anti-neutrophil cytoplasmic antibodies (ANCA). Nerve conduction studies (NCS) showed patchy non-length dependent motor and sensory large fiber axonal polyneuropathy in lower limbs. Sural nerve biopsy showed non-granulomatous perivascular T-cell inflammation diagnostic of microvasculitis. Her vasculitis was thought to be secondary to cocaine use. She was started on high dose steroids followed by a taper showing clinical improvement.
Conclusion: Cocaine as a cause of acute multifocal polyneuropathy should be considered in the setting of drug abuse.
P-16 A 58-Year-Old Woman with a Painful Mimic of AIDP
C. Sanderson, S. Bhai, Dallas, TX.
Seven months prior to presentation, she had abrupt, new-onset abdominal pain, nausea, and anorexia resulting in weight loss of 20 pounds. The etiology was unclear, but resulted in a cholecystectomy, which did not provide relief. One week after surgery, she began having paresthesias in her fingers and toes, spreading more proximally over the subsequent 2 weeks. She had marked pain as well as irritability, anxiety, and difficulty walking. These symptoms continued without progression with cyclical episodes of nausea and vomiting. Diagnoses of Guillain-Barré syndrome and Multiple Sclerosis were considered. She then presented to UT Southwestern for further evaluation. At that time, she denied vision changes, dysphagia, dyspnea, and recent viral illness or vaccines. She previously had breast cancer (11 years prior) without known recurrence and cervical spine decompression. She used alcohol and tobacco daily. No illicit drugs. No family history of neurologic or metabolic disorders. Medications include pregabalin, sertraline, and opiates. Exam was significant for normal skin, cranial nerve, reflex, and cerebellar exams. Motor exam revealed bilateral elbow extension (4/5) and hip flexion weakness (4/5). There were no fasciculations. Sensory exam showed decreased pinprick and vibration in a length-dependent manner. There was no sensory level. She required assistance to stand and walk safely due to balance dysfunction and weakness. Work-up included labs for neuropathy, inflammatory and autoimmune conditions, and infections, all of which were unremarkable, except for a mild SSB elevation. MRI Brain showed a FLAIR hyperintense lesion in the left frontal corona radiata, and her MRI cervical and thoracic spine were unremarkable. NCS showed a mild length-dependent sensory axonal neuropathy with normal EMG. A diagnostic test was then sent, treatment was started, and her symptoms improved.
P-17 Painful Bilateral Asymmetric Proximal Leg Weakness
M. Kim, T. Thuyphuong Nguyen, Houston, TX.
Introduction: Peripheral nervous system diseases leading to significant morbidity within a time frame of 2 weeks have a restricted differential diagnosis. We report a case of painful nerve root involvement due to diffuse B-cell lymphoma.
Methods: We report a case of a 58-year-old man referred to neuromuscular clinic for EMG for bilateral leg weakness leading to inability to walk in a time frame of 2 weeks.
Results: Patient first noticed aching pain in the left flank and hip after he worked under the sink for hours. One week later, he developed severe aching pain, weakness, and tingling in the right hip and knee. He began to use a wheelchair the following week as he developed left leg weakness. He denied bowel/bladder incontinence, urinary retention, or saddle anesthesia. Motor exam showed 1–2 out of 5 in the bilateral hip flexors, adductors, and knee extensors. Sensory exam was normal, despite subjective tingling. Bilateral knee and ankle reflexes were hyporeflexic. EMG/NCS showed severe, asymmetric acute neurogenic changes, predominant in L3 and/or L4 myotomes. Differential diagnosis included lumbar plexopathy or lumbar polyradiculopathy. MRI lumbar spine without contrast was reportedly unremarkable. Patient was admitted, and MRI spine with contrast showed enhancing marrow replacing osseous lesions in the S2-S4 bodies with associated cauda equina nerve root enhancement. MRI brain showed calvarial metastasis in the right frontal bone. He underwent CT-guided biopsy of the sacral and left femoral head bone lesions which revealed diffuse large B-cell lymphoma. PET CT showed lymphoma in the thyroid, lungs, mediastinum, large and small bowel, gallbladder, and right kidney. He received R-CHOP and radiation therapy with improvement in hip adductors strength. He also developed bilateral Bell's palsy which was deemed as disease progression.
Conclusions: This case highlights a rare presentation of lymphomatous polyradiculopathy presenting with inability to walk within 2 weeks.
P-18 Advances in SMA treatment, a Consideration
M. Varnet, D. Castro, K. Goodspeed, Dallas, TX.
We present 2 cases of Spinal Muscular Atrophy (SMA) with reduced motor disability on Nusinersen who were diagnosed with autism spectrum disorder (ASD). ASD is a developmental disorder with restricted/repetitive behaviors and social communication deficits that affects 1 in 44 children. Without treatment, children with SMA, a severe motor neuron disease, succumb to their disease before manifesting symptoms of ASD. Because treatments for SMA prolong life and reduced motor disability, additional developmental disabilities may be identified. ASD is a developmental disorder with restricted/repetitive behaviors and social communication deficits that affects 1 in 44 children. Without treatment, children with SMA, a severe motor neuron disease, succumb to their disease before manifesting symptoms of ASD. Because treatments for SMA prolong life and reduced motor disability, additional developmental disabilities may be identified. We describe 2 patients receiving treatment for SMA diagnosed with ASD. Patient 1 was unable to move his limbs at 3.5 weeks old and Patient 2 was unable to sit unsupported at 6-months old. They were diagnosed with SMA type 1 and 2, respectively. Each demonstrated motor gains with initiation of Nusinersen. Patient 1 sits independently and feeds by mouth, and Patient 2 has continued to gain strength with age. Around 5-years old, each were noted to have autistic traits including stereotyped hand movements and difficulty with social reciprocity. Patient 1 struggled with emotional regulation and distractibility. Patient 2 had poor eye contact and delayed language without compensatory nonverbal behaviors. A comprehensive cognitive and behavioral assessment revealed low verbal reasoning and spatial abilities in both patients. Autism testing using the Childhood Autism Rating Scale and Behavioral Observation Scale for Autism were consistent with mild to moderate ASD for both with concern for inattentive-type ADHD in Patient 1. Behavioral therapy was recommended to improve delays in social communication and play skills. Children receiving precision therapy for SMA should be screened for common neurodevelopmental disabilities. Patient 1 (SMA1) had prolonged lifespan and Patient 2 (SMA2) had improved motor function; each able to manifest autistic traits because of treatment for SMA. Screening is important because as in SMA, early recognition and intervention improves outcomes in ASD.
P-19 An Uncommon Cause of a Common NMJ Disorder
D. Shah, S. Bhai, J. Elliott, Dallas, TX.
Objective: To describe a rare case of a congenital neuromuscular junction disorder.
Introduction: Congenital myasthenic syndromes (CMS) are a genetically and phenotypically heterogenous group of disorders in which neuromuscular junction transmission is impaired. Patients are often misdiagnosed with seronegative myasthenia gravis. Early diagnosis can prevent unnecessary exposure to immunotherapy.
Case Description: A 23-year-old woman presented with diffuse fatigable weakness, drooping of eyelids, double vision, difficulty swallowing and breathing. There was no family history of neuromuscular disease. Her neurological examination was pertinent for ophthalmoparesis, bilateral fatigable ptosis, and facial, tongue and proximal extremity weakness. She was admitted due to respiratory decline, requiring intubation. She was treated with 6 sessions of plasma exchange and was able to be extubated. She was then treated as an outpatient with prednisone, pyridostigmine, and IVIG infusions as well as therapeutic doses of mycophenolate mofetil, but continued to have symptoms. CK, TSH, lactate, and pyruvate levels were unremarkable. Antibodies to acetylcholine receptor, MuSK, LRP4, striated muscle, P/Q type and N-type voltage-gated calcium channels were negative. Three Hertz repetitive nerve stimulation of the right spinal accessory and facial nerves and single fiber EMG of the right frontalis muscle showed evidence of a post-synaptic neuromuscular junction disorder. Early recruitment of small motor units was seen on EMG. CT chest was negative for thymoma. Sleep study showed moderate obstructive sleep apnea. Genetic testing confirmed the presence of autosomal recessive pathogenic mutations in the MuSK gene, confirming the diagnosis of a post-synaptic CMS. Discussion: CMS due to MuSK gene mutations are exceedingly rare. The pathogenic MuSK mutation seen in our patient has been reported in several individuals affected with CMS. Frameshift mutations cause absence of MuSK expression. Missense mutations lead to decreased MuSK expression and stability, leading to reduced acetylcholine receptor aggregation. Symptomatic treatment with albuterol, ephedrine or 3,4-diaminopyridine can be tried.
P-20 A Girl with Hypotonia, Neck Flexion Weakness & White Matter Changes
I. Mak, S. Novara, A. Hurst, N. Rudy, M. Lopez, Birmingham, AL.
A 5-year-old girl presented with a history of developmental delay, torticollis, and poor head control starting from 4 months old, but able to attain head control at 10 months old. Magnetic resonance imaging (MRI) of the brain identified increased T2-hyperintensities in the periatrial white matter. She had delayed motor milestones with preserved speech and social skills. For example, she had poor head control, delayed unassisted walking, and clumsiness with fine motor tasks. At 21 months old, she had moderate hypotonia with distal joint laxity in her hands. Her head control improved, but was still weak. Over 3 years, she made developmental progress, but continued to have problems with running, climbing stairs, and pain after exertion. At age 4 years, she had difficulty with chin tuck and sitting unassisted. She transitioned from sitting to standing by Gowers' maneuvers. At age 5 years, she continued to have hypotonia, neck flexion weakness, and 4 out of 5 strength throughout upper and lower extremities. Gait showed a lordotic stance, over-pronated feet, and waddling. She had no ptosis, ophthalmoplegia, facial weakness, or dysmorphisms. Sensation, myostatic stretch reflexes, and coordination were normal. A second MRI brain at 19 months old demonstrated slightly increased T2 signal abnormalities in parietal and occipital periatrial regions, which remained stable a year later. Her acylcarnitine, acylglycine, plasma amino acids, creatine kinase, enzyme analysis for lysosomal storage disorders, and chromosomal microarray were normal. A Next Generation Sequencing panel of 109 genes associated with neuromuscular disorders revealed a homozygous pathogenic variant confirming the molecular diagnosis. This case illustrates previously reported features of hypotonia and neck flexion weakness that manifested early and subsequently progressed to involve extremities. However, the white matter changes have not been described previously in this congenital myopathy and may represent an under-reported phenotypic finding.
P-21 A Case of Asymptomatic HyperCKemia
A. Tajuddin, M. Dimachkie, O. Jawdat, D. Jabari, C. Farmakidis, S. Chandrashkhar, M. Pasnoor, Kansas City, KS.
Introduction: The ANO5 gene encodes anoctamin-5 which has a chloride channel function and is involved in cell membrane maintenance and repair. ANO5 gene mutations have been associated with muscle disease and skeletal abnormalities. The phenotypic spectrum ranges from asymptomatic hyperCKemia, exercise-induced myalgia, gnathodiaphyseal dysplasia to limb-girdle muscular dystrophy type 2L (also known as R12) and distal muscle weakness as in Miyoshi-like myopathy 3.
Methods: We describe a case of asymptomatic hyperCKemia associated with heterozygous ANO5 gene deletion.
Case Report: A 19-year-old male presented with 1-year history of incidentally discovered high creatine kinase (CK). In the work up of EBV-associated liver injury, elevated transaminases led to measurement of CK, initially 2732 IU/L. Since then, CK values ranged from 2955 to 25,000 IU/L. After 2 weeks of exercise avoidance, CK was 7100. He is athletic and has no history of myalgia or muscle weakness and no family history of muscle disease. Neuromuscular examination revealed mild bilateral toe flexion and extension weakness. Muscle bulk was normal without myotonia, myoedema, or muscle rippling. Metabolic and inflammatory markers were normal including myositis specific antibodies, HMGCR antibody, carnitine and acylcarnitine profiles. NCS/EMG study showed mild chronic irritative myopathy. Thigh muscle MRI scan showed subtle edema with enhancement involving the bilateral adductors and anterior thigh muscles. Targeted NGS muscle panel through Perkin Elmer showed heterozygous changes in ANO5. There was deletion of the whole ANO5 gene from exon 1 to 22. In addition, there was a variant of unknown significance (VUS) in ANO5 at c.1924C > G (present in 0.01% of the general population, and in silico analyses imply potentially deleterious effect) and another VUS in ITGA7. Left vastus lateralis muscle biopsy showed necrotizing myopathy with prominent myofiber necrosis and regeneration.
Conclusion: We raise awareness of ANO5 presenting as asymptomatic hyperCKemia and its association with necrotizing myopathy histopathology.
P-22 FORCETM Platform for Treating Muscle Diseases
C. Desjardins, T. Picariello, S. Zanotti, S. Spring, Q. Qiu, T. Weeden, M. Roy, J. Davis, S. Hilderbrand, Waltham, MA.
Lack of targeted delivery of oligonucleotide therapeutics to muscle tissues remains a challenge in the treatment of muscle diseases. The FORCETM platform, designed to overcome these limitations, consists of an oligonucleotide payload conjugated to an antigen-binding fragment (Fab) targeting the extracellular region of the human transferrin receptor (TfR)1 which is expressed in muscles. This allows for the rational selection of payloads to target the genetic basis of disease. FORCE-M23D, a Fab-conjugated phosphorodiamidate morpholino oligomer (PMO) designed to skip exon 23 was evaluated in mdx mice, a model of Duchenne muscular dystrophy (DMD). Additionally, Dyne's clinical candidate, DYNE-251, an exon 51 skipping conjugate, was tested in non-human primates (NHPs). In myotonic dystrophy 1 (DM1), DYNE-101, a Fab-conjugated antisense oligonucleotide (ASO) was assessed for its ability to knock down toxic human DMPK RNA using a hTfR1/DMSXL mice representing severe DM1. Safety was assessed in NHP GLP (DMD) and non-GLP (DM1) toxicology studies. A single dose of FORCE-M23D achieved dose-dependent, robust, and durable exon skipping and dystrophin restoration in muscle of mdx mice. At 4 weeks, 30 mg/kg of FORCE-M23D led to 78%, 90%, and 46% of wild-type dystrophin restoration by Western blot in the heart, diaphragm, and quadriceps, respectively, with 68% dystrophin-positive fibers in quadriceps. DYNE-251 demonstrated robust exon 51 skipping in cardiac and skeletal muscles of NHPs and was well-tolerated. Administration of DYNE-101 to hTfR1/DMSXL mice resulted in robust and durable knockdown of human toxic nuclear DMPK RNA in muscle tissues. A single dose of DYNE-101 delivered sustained reductions in toxic human DMPK RNA (49%) and foci area (49%) in heart tissue leading to splicing correction at 4 weeks. Similar knockdown and correction of splicing were observed in skeletal muscle at 4 weeks. DYNE-101 was well tolerated in NHPs. These data validate the FORCE platform for developing therapeutics for muscle diseases.
P-23 Infant with Arthrogryposis and Developmental Delay
A. Webb, S. Moody, Houston, TX.
Purpose of Study: To describe a case of a patient with a rare congenital myopathy and review relevant literature.
Methods: Case report.
Results: A 1-year-old female of Middle Eastern descent born at term with multiple congenital anomalies including arthrogryposis, bilateral talipes equinovarus, clenched fists, cleft palate, micrognathia, and hearing loss was referred to neurology for evaluation of developmental delay. Her medical history is significant for cardiac arrest during surgical repair of cleft palate at 11 months, scoliosis, and gastric tube dependence. Her parents are first cousins and the family history is significant for hearing loss in her father and brother. At 7 months she was able to sit without support, but at 1 year she was unable to roll over, crawl, stand, or walk. She consistently used one word correctly. The physical exam demonstrated dysmorphic facial features with bitemporal narrowing, small downturned eyes, downturned upper lip, long eyelashes, prominent cheeks, bulbous nose, cupped ears, and a small recessed chin. Neurologic exam showed OS ptosis and decreased facial movements with intact sensation to light touch in all extremities. The motor exam was significant for hypotonia in all extremities, axillary slippage, and head lag. She was unable to hold her head up independently while prone. MRI of her brain at 2 weeks of age demonstrated small bilateral subdural hematomas without mass effect. MRI of her spine showed S-shaped curvature of the thoracolumbar spine. Chromosomal microarray showed absence of heterozygosity but no deletions or duplications identified. Further genetic testing with whole exome sequencing revealed variants consistent with her clinical presentation. Clinical features and management of this condition will be discussed.
Conclusion: Bailey-Bloch congenital myopathy is a rare cause of inherited myopathy with susceptibility to malignant hyperthermia. It is important to identify this condition early in order to effectively guide treatment.
P-24 Child with Recurrent Rhabdomyolysis
A. Webb, S. Moody, Houston, TX.
Purpose: To describe a patient with recurrent rhabdomyolysis and review the diagnosis and relevant literature.
Methods: Case report.
Results: An 18-month-old Caucasian female presents for evaluation after 2 episodes of rhabdomyolysis requiring hospital admission at 13 months and 16 months of age. She has no relevant past medical history but does have a family history of amyotrophic lateral sclerosis in multiple paternal family members. Both episodes of rhabdomyolysis were preceded by symptoms of an upper respiratory infection for several days prior to admission. She was noted to have decreased activity with refusal to bear weight, tenderness to palpation of bilateral lower extremities, and dark colored urine. Development was normal without regression of motor milestones. Neurologic exam showed increased tone in bilateral lower extremities but reflexes and strength were normal in all extremities. Labs were significant for an unmeasurably high creatine kinase (CK) greater than 41,000, elevated liver enzymes, myoglobinemia, and myoglobinuria. Echocardiogram was normal. She was treated with intravenous hydration and returned to neurologic baseline with normalization of CK levels within 1 week following both admissions. Additional work-up including acylcarnitine profile, urine organic acids, plasma amino acids, pyruvate, thyroid function studies, and lactate were unremarkable. Two muscle biopsies obtained from the left vastus lateralis showed congenital muscle fiber type disproportion with type I fibers smaller than type II. Biochemical analysis revealed borderline deficiency of phosphorylase b kinase but no definitive diagnosis was reached. Mitochondrial gene testing was unremarkable. Further testing subsequently revealed a genetic etiology for the patient's symptoms.
Conclusion: In pediatric patients presenting with recurrent rhabdomyolysis, LPIN1 gene mutations are important to consider as part of the differential. Early diagnosis can help physicians tailor prophylactic treatment during times of catabolism to minimize risk of rhabdomyolysis recurrence.
P-25 An Intriguing, Engaging Spells/Falls Case
E. Martinez-Alvernia, Austin, TX.
A 59-year-old-male presents to our clinic with the chief complaint of seizure-like episodes. The spells started approximately 8 months ago subsequent to a gallbladder surgery. The first episode occurred while standing in the kitchen, he went stiff and fell backwards. There was no tongue biting or incontinence. He woke up to his wife doing CPR. He was transported to ER, where he was found to be dehydrated. He was given potassium pills, fluids with improvement. At the time, brain imaging was negative. Reports having 6 total spells over 8 months. Denies aura/warning or postictal-confusion with these episodes. He went to a neurologist who ordered an MRI brain and EEG, both of which were unremarkable. The patient saw cardiology, who found him to be having SVTs. He then underwent loop recorder implantation. He was unable to get out of bed due to severe dizziness and spells, and was found to be in V-Tach, with prolonged QT waves (534msc). His potassium level was found to be very low at 0.9. He was started on magnesium and potassium, but his electrolyte levels were difficult to stabilize. A defibrillator was implanted and he was released on vitamin/supplements. Currently he feels well and has gone several months without a spell. Discussion: On the differential we certainly have Andersen–Tawil syndrome (ATS) a rare hereditary multisystem disorder. Ventricular arrhythmias, Periodic Paralysis (PP) and dysmorphic features constitute the classic triad of ATS symptoms and is associated with a loss-of-function mutation in the KCNJ2 gene, which encodes the Kir2. Common features of PP include autosomal dominant inheritance, episodic attacks of flaccid weakness, which are often triggered by diet or rest after exercise. The patient exhibits dysmorphic features as clinodactyly and syndactyly, so we ordered genetic testing.
P-26 A Case of an Infant with Hypotonia
C. Chan, R. Bhavaraju-Sanka, S. Atkinson, San Antonio, TX.
Objectives: Describe a case about a patient presenting with hypotonia at birth.
Background: Hypotonia can present as early as infancy. This can be benign like in benign congenital hypotonia, or this can be related to a variety of conditions, including those that involve the central nervous system, muscle disorders, and genetic disorders.
Design/Method: Case Report.
Results: A late preterm infant who had poor tone at delivery and required respiratory support was admitted to the Neonatal Intensive Care Unit (NICU). He was on non-invasive positive pressure ventilation and could not tolerate high-flow nasal cannula. Physical exam was significant for low-set ears, microganthia, high-arched palate, weak suck, absent rooting reflex, profound head lag, and diffuse hypotonia. Patient's mother was noted to have mild proximal weakness, ptosis, and limited prenatal care during pregnancy, which was also complicated by polyhydramnios and preterm premature rupture of membranes. Delivery was without complication. A head ultrasound showed no evidence of intracranial hemorrhage. Newborn screen was negative. The patient at 5 weeks had persistent oropharyngeal dysphagia. Acetylcholine receptor blocking and binding antibodies, Angelman, Prader-Willi were negative. The patient was trialed on intravenous immunoglobulin (IVIG) 2 g/kg divided over 5 days with improvement in bilateral upper and lower extremity tone. The patient continued to have oropharyngeal dysphagia and required gastric tube placement at 13 weeks old.
Conclusion: This case demonstrates a rare condition causing hypotonia in an infant. As the patient's mother exhibited symptoms of myasthenia gravis, transient neonatal myasthenia gravis was considered. However, this typically responds to pyridostigmine with improvement overtime. This patient had persistent oropharyngeal dysphagia despite pyridostigmine, raising concern for fetal acetylcholine receptor inactivation syndrome (FARIS). He had some modest response to Albuterol. At 5 months old, he had improvement in extremity tone but continued to have neck hypotonia.
P-27 Exertional Myalgia in a Middle-aged Male
S. Liles, M. Zulfiqar, S. Shukla, Jackson, MS.
Background: Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder that prevents the removal of carnitine from long-chain fatty acids inside mitochondria, effectively inhibiting long-chain fatty acid oxidation. This allows for accumulation of fatty acids and long-chain acylcarnitines in skeletal muscle and other organs. It can present as a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form. The myopathic form is much less severe than other types of CPT II deficiency and is characterized by recurrent episodes of myalgia associated with rhabdomyolysis causing myoglobinuria. These episodes may be triggered by exercise, stress, fasting, infections, or exposure to extreme temperatures, and patients may remain asymptomatic between episodes.
Case: A 57-year-old Caucasian male was followed in clinic with generalized myalgia and mild proximal weakness in the shoulders (MRC 4/5) and hip flexors (MRC 4/5). He had a history of low back pain and prior diagnosis of unspecified metabolic myopathy. Patient reported episodes of exertional myalgia and weakness since childhood, and prior documentation showed elevated Creatine kinase (CK) and myoglobinuria. Similar symptoms were noted in his father and brother, both of whom are now deceased. On initial visit, aldolase and CK were elevated to 8.1 and 293 respectively; on follow-up visit, aldolase and CK were extremely elevated to 10.7 and 4049 and serum myoglobin was >5000. Magnetic resonance imaging (MRI) of cervical and lumbar spine showed degenerative changes. A metabolic myopathy panel showed 2 heterozygous mutations in the CPT II gene, on exons 3 and 5. Parental testing for cis/trans was unable to be performed as both were deceased. A specific myopathic disease was diagnosed based on clinical features, biopsy, biochemical and genetic testing.
Conclusions: Early recognition and diagnosis of CPTII mitochondrial myopathy can assist in management through implementing lifestyle and diet changes to avoid episode triggers.
P-28 Adulthood Milestones in (OMIT)
V. Czerwinski, A. Veerapandiyan, D. Guntrum, E. Ciafaloni, J. Statland, Kansas City, KS.
Objective: Increase the understanding of adult life outcomes in individuals with Becker and Duchenne Muscular Dystrophy.
Background: Dramatic changes in the natural history of Duchenne and Becker muscular dystrophy (D/BMD) has resulted in individuals who previously died in their teens now regularly living into their 30 s. Given the increased life expectancy, the medical community is now faced with helping these individuals transition into adulthood; however, the state of adulthood outcomes in B/DMD patients in the US is largely unknown.
Methods: We administered a cross-sectional survey to 48 men ages 16–59 with B/DMD. Subjects were recruited from “The Duchenne Registry” as well as 3 clinical sites. Our 102-question survey assessed body function, housing, education, employment, transportation, relationships, and transition planning.
Results: Most individuals enrolled had Duchenne (44, 92%). Of adults with Duchenne, 64% lived in urban environments and 68% lived with their parents. On average, most of their day is spent watching television (3.7 hours/day) or on the computer (6.5 hours/day). Many (66%) own their own van. One third (38%) do not have personal care assistants outside their family members. The majority have completed highschool, and over half (53%) have completed at least some college. Eight are in relationships, and the majority who are not in relationships believe romantic relationships to be unobtainable. Sixteen of the participants work, and “Computer/IT” is the most represented field. One quarter (23%) reported having a transition plan. Only 4 had this plan written out.
Conclusions: Our results reaffirm a commonly held belief-that those with B/DMD can go on to live fulfilling and productive lives; however, the findings also highlight the inadequacies of providers to establish transition plans and help young men with B/DMD gain competencies for their adult social lives.
P-29 Late Onset Progressive Proximal Weakness
I. Bakk, C. Farmakidis, M. Dimachkie, Kansas City, KS.
Objective: To describe novel presentation of proximal weakness.
Case Presentation: A 69-year-old retired teacher originally presented with a 5-year history of progressive difficulty keeping her head up, generalized weakness with decreased activity tolerance, and mild symmetric ptosis initially only noted by her ophthalmologist. Prior to symptom onset the patient had no neurologic history and was highly functional. She denied any difficulty chewing or swallowing. There is no family history of similar weakness, periodic weakness, or other known neuromuscular disease. There is also no known history of complications with anesthesia. Physical examination was notable for mild bilateral ptosis without fatigability on upward gaze. Strength testing revealed proximal weakness in the neck and upper and lower extremities. The gait examination revealed wide-based shuffling with head drop. Serum testing noted negative AChR and MuSK antibody. Electrolyte and creatine phosphate kinase levels were normal. EMG showed mixed large and small MUAPs that suggested myopathy. Repetitive nerve stimulation was non-diagnostic. Muscle biopsy of the right vastus lateralis showed neurogenic atrophy with no myopathic changes, inflammation, or vasculitis. Whole exome sequencing revealed a heterozygous pathogenic variant on CACNA1S (c.520C > T, p.R174W). Patient was offered a prednisone and pyridostigmine trial without benefit. She was offered acetazolamide trial with some benefit. Literature: The c.520C > T, p.R174W CACNA1S variant has been seen in multiple individuals including family members with malignant hyperthermia, but it has never been associated with fixed myopathic weakness.
Conclusion: Fixed weakness without periodic paralysis is a rare manifestation in pathogenic CACNA1S and to our knowledge has never been reported with the c.520C > T variant. The patient should be advised that she may be at increased risk of developing malignant hyperthermia.
||When Pes Cavus is not Charcot-Marie-Tooth
||Ataxia with oculomotor apraxia type 2
||Lifelong Diagnosis of a Functional Gait
||Childhood Bulbar Dysfunction and Weakness
||Presumed Kennedy's Disease, confirmation pending
||A Curious Case of Ptosis and Bulbar Weakness
||Leptomeningeal carcinomatosis (Sezary syndrome)
||Novel Target to Treat Congenital Hypotonia
||LAMA2 muscular dystrophy
||Developmental Delay & Supraventricular Tachycardia
||Megaconial muscular dystrophy
||Frequency of Cancer in Myotonic Muscular Dystrophy
||Myotonic Muscular Dystrophy
||Pain Profile and Opioid Medication Use in Myositis
||Use of Mexiletine in Childhood Myotonic Dystrophy
||Tendon Transfers in IBM: Systematic Review
||Cardiomyopathy in Friedreich's Ataxia Patients
||Myasthenia Gravis and COVID 19: Case series
||Biking Induced Kinetic Electroshock Syndrome
||POTS or Not? A Rare Diagnosis Mislabeled as POTS
||Rapidly Progressing Myopathy in a Toddler
||Myopathy from MELAS gene mutation
||A Rare Presentation of Inflammatory Myositis
||NXP-2 Positive Dermatomyositis
||A Rare Cause of Progressive Myopathy
||Isolated Granulomatous Myositis
||Neuromuscular Disease Due to Checkpoint Inhibitor
||Immune-mediated necrotizing myopathy + Myasthenia
||Impaired Large Fiber Sensory Exam with Normal NCS
||PIEZO 2 mutation causing impaired mechanoreceptors
||36-year-old Man with Episodes of Rhabdomyolysis
||Phase 2/3 Study of Arimoclomol in IBM
||Inclusion Body Myositis
||An Unusual Case of Episodic Weakness
||Suspect mtATP6/mtATP8 mutation, pending testing
||Patient and Physician Perspectives on gMG Care
||Same Story, Different Ending - Case Reports
||Lower limb spasticity presentations
||Limb-Girdle Weakness and Isolated Finger Extension
||Late Onset Neuropathy: Hereditary Vs. Acquired
||MZP related peripheral neuropathy neuropathy
||Outcomes After PEG Intervention in ALS patients
||Delayed Diagnosis in Pediatric CMT
||Acute Polyneuropathy in Patients with Weight Loss
||Partially Purple Pedis Problem
||Livedoid vasculopathy causing mononeuritis multiplex
||COVID Spike Antibodies in Neuromuscular Condition
||Rare Cause of Brachial Diplegia
||Cervical spine hemangioblastoma
||A Rare Cause of Acute Unilateral Foot Drop
||Sciatic neuropathy due to lymphomatous lesion
||CMT 2Q disease
||Effects of Cocaine on Peripheral Nervous System
||Cocaine Induced Vasculitic Neuropathy
||A 58-year-old Woman with a Painful Mimic of AIDP
||Acute intermittent porphyria
||Painful Bilateral Asymmetric Proximal Leg Weakness
||Advances in SMA treatment, a Consideration
||Autism and SMA
||An Uncommon Cause of a Common NMJ Disorder
||Congenital myasthenic syndrome
||A Girl with Hypotonia, Neck Flexion Weakness & White Matter Changes
||A Case of Asymptomatic HyperCKemia
||ANO5 presenting as asymptomatic hyperCKemia
||FORCETM Platform for Treating Muscle Diseases
||Infant with Arthrogryposis and Developmental Delay
||Bailey-Bloch congenital myopathy
||Child with Recurrent Rhabdomyolysis
||LPIN1-related recurrent rhabdomyolysis
||An Intriguing, Engaging Spells/Falls Case
||Andersen-Tawil Sd versus Hypokalemic PP
||A Case of an Infant with Hypotonia
||Fetal acetylcholine receptor inactivation syndrome
||Exertional Myalgia in a Middle-aged Male
||CPT II Mitochondrial Myopathy
||Adulthood Milestones in (OMIT)
||Duchenne Muscular Dystrophy
||Late Onset Progressive Proximal Weakness
||Proximal weakness with CACNA1S (c.520C > T variant)